Document 2062
 DOCN  M94A2062
 TI    Synthetic peptides from the V3 loop modulate HIV-1 infection.
 DT    9412
 AU    Zanotto C; De Rossi A; Calderazzo F; Cabrelle A; Dettin M; Di Bello C;
       Chieco-Bianchi L; Inst. Oncology, University of Padova, Italy.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):39 (abstract no. 131A). Unique
       Identifier : AIDSLINE ICA10/94370513
 AB    OBJECTIVE: It has been demonstrated that a 23-mer peptide (DB3) derived
       from the V3 loop of MN strain enhances HIV-1 infection (Virol. 1991;
       184, 187, Biochem. Biophys. Res. Commun. 1993; 191, 364). We have
       studied the mechanism and structural features required for this
       biological effect. METHODS: DB3 analogues with a single amino acid
       substitution and shortened derivatives were prepared. MOLT-3 cells were
       infected with HIV-1 in the presence of scalar dilutions of these
       peptides. HIV-1 p24 antigen levels in supernatants were determined by an
       Elisa assay. Expression of CD4 molecules on the peptide-treated cells
       was quantitated by cytofluorimetric analyses. Soluble CD4-gp120 Elisa
       assays were performed in the presence of scalar dilutions of the
       peptides. RESULTS: We found that the substitution of Lysine with
       Asparagine near the C-terminus (peptide DB3-Asn19) increased the
       enhancing effect of DB3 while the replacement of any other positively
       charged amino acid decreased the peptide's activity on viral infection.
       Peptides in which an aromatic amino acid was changed to Isoleucine,
       peptides with D-amino acids, and shortened derivatives of DB3, did not
       show any enhancing effect. DB3 and DB3-Asn19 enhanced CD4 expression and
       gp120 binding to soluble CD4; all other tested peptides did not.
       CONCLUSIONS: These results suggest that the effect of DB3 on the viral
       infection process is influenced by the presence of positively charged
       and aromatic amino acids and by the conformation of the primary
       sequence. Moreover, this activity appears to be mediated by an increase
       in CD4 expression and/or CD4-gp120 binding affinity.
 DE    Amino Acid Sequence  Antigens, CD4/ANALYSIS  DNA-Binding
       Proteins/PHARMACOLOGY  Enzyme-Linked Immunosorbent Assay  Flow Cytometry
       HIV Core Protein p24/IMMUNOLOGY  HIV Envelope Protein
       gp120/ANALYSIS/METABOLISM  HIV-1/*GENETICS
       Peptides/*GENETICS/PHARMACOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).